The overall objective is to provide a structural basis for understanding how certain tumors are caused by ras oncogene products. The specific objective of this proposal is to determine the 3dimensional structures of three classes of ras oncogene products, K-, H, and Nras proteins, by Xray diffraction methods. In each class there are three types of proteins: viral, normal cellular, and activated cellular ras proteins. These structures may (a) provide a basis for understanding the biochemical differences between normal and activated cellular ras gene products; (b) suggest other functional roles (including the normal cellular functions) of the ras proteins; (c) reveal the possible conformational changes on guanine nucleotide binding; and (d) lay a foundation for rational designing of the ligands that could modulate known biochemical functions of the ras proteins.